Esters of amino alcohols and process for producting them



Patented et.f2 9, i I I 2,2193% UNITED .STATES PATENT OFFICE ESTERS 0F AMINO ALCOHOLS AND PROCESS FOR PRODUCING THEM Pierre Viaud, Paris, France, assignor to Societe Des Usines Chimiques Rhone-Poulenc, Paris, France, a body corporate of France No Drawing. Application October 9, 1937, Serial No. 168,196. In Great Britain October 16, 1936 3 Claims. (Cl- 260-477) This invention relates to the manufacture of cooled and the hydrochloride formed is drained 8. new ester of an amino alcohol having interestand washed with benzene. The hydrochloride ing therapeutic properties.

It is known that the phenyl-substituted fatty V 5 acid esters of certain branched chain aliphatic CECOOCHWH: 5v

amino-alcohols possess antispasmodic action and Com also that basic esters of polyary a acids 1 is thus obtained and has m. p. 109 c. The free sess an action of the same kind. It hasnow been base h b of 140.444? 1-, 3 of found that esters of a-phenylaliphatic acids and N-disubstituted-amino-normal-aliphatic alcohols Example 2 have marked spasmolytic properties, while having Into a 500 cc. flask with three necks provided at the same time a particularly slight toxic acwith a mechanical stirrer and a reflux condenser .ti are introduced 0.1 gram molecules of dry potassi- The object of the present invention is the prepum a-phenyl butyrate and 75 cc. of dry benzene, aration of a compound in which the toxic and and then a solution of 0-1 gram molecules of dithe curativedoses are more widely separated than ethylaminochlorethane: CI.CH2CH2N(C2H5) z in in the known products. According to the present 50 cc. of dry benzene. The mixture is heated for invention, it has been ascertained that the afour hours under reflux with stirring. The minphenylvalerate of diethylaminoethanol has an era] salts are separated by washing with water especially strong spasmolytic action, both neuroand the product then rectified by distillation. tropic and musculotropic, while at the same time The amino-ester formed 20 its toxicity is minimum, so that it is particularly czmcfl'coQCHNHLMCIH), useful in medicinal usage. I

According to the present invention the aphenyl-valerate of N-diethylaminoethanol can be boils at undel 7 0 e prepared either by esterification of a-phenylhydrochloride melts at 25 valeric acid with diethylamino-ethanol or by'the Example 3 action of the chloride or anhydride of the acid on diethylaminoethanol or by the action of the 0.2 gram molecules of' diethylamlne and 04.1 kali salts of a-phenylvaleric acid on l-diethylgram 1111eu1e$ of fi-chbrethyl-u-phenylbutyraie 30 amino-z-chlorethane or by the action of diethyl- CzH5.CH.COOCHzCHzCl amine on the ester formed from a-phenylvaleric (m and are mixed, and the mixture is heated in a sealed Ewample 1 tube for 13-14 hours at 100 C. After cooling it 35 In a threemecked fla k fitted with a reflux is taken up with a mixture of ether and 5% hy- 35 condenser and a stirrer is placed 0.1 gram drochloric acid. The ether is separated from the 180mm. proportions f m aqueous acid and the latter is rendered alkaline ride by the addition of sodium carbonate; The ami- 40 C3H7 no-ester is then extracted from the alkali lye with 40 ether; the ethereal solution is washed with water, CH C0C1 dried and rectified. The a-phenyl-butyrate of 7 diethylaminoethanol previously describedis thus dissolved in 50 cc. of dry benzene. obtained" 0.1 gram molecular proportions of dieth -mmple. 4 45 aminoethanol dissolved in cc. of dry benzene 0.1 gram molecules of m-phenylbutyric -acid, 0.1 are introduced in small quantities at a time durgram molecules of the hydrochloride of diethyling about 10 minutes with stirring. aminochlorethane, 0.15 gram molecules of anhy- The mixture is heated for 3 hours at C. on drous potassium carbonate are mixed with 25 cc. Y 50 the water-bath with stirring. The product is acetone. The mixture is heated under a reflux 50 CaHs uHs

' cnncircoocmcmcmmclmh CzH CHQC O O .CILGHzCHrCHzNUJzHs):

C tHB C aHs CgHa CtHt

Example 0.11 gram molecules of u-phenylbutyric acid, 0.10 gram molecules of diethylaminoethanol, 80 cc. xylene and 0.13 gram molecules of benzene sulphonic acid are mixed in a three-necked flask of 500 cc. provided with a mechanical stirrer, a tap funnel and a rectifying column acting as a condenser. The mixture is boiled for 4 hours and about 500 cc. xylene is distilled 011. A quantity of xylene equal to that distilled is added bit by bit. At the end of this time the xylene solution is washed with a solution of sodium carbonate to remove the a-phenylbutyric acid which has not reacted. The mixture is then heated for three hours under a reflux condenser. After cooling, the mixture is extracted with 5% hydrochloric acid, and this solution extracted again with ether. The free amino-ester is liberated by the addition of 35-40 grams of sodium carbonate, extracted with ether, and the ethereal solution washed with water, dried and rectified. The amino-ester of formula:

011.0 0 O.CH1.CH:.CH.N(CIHI)3 CqHs is obtained as an oil of b. p. 151155 C. at 2 mm. of Hg.

The following esters are likewise prepared according to the present invention:

B. P. 140-142 C. at 4 mm. Hg. M. P. of methiodide: 8082 C.

}B. P. 149-151" C. at 3 mm. Hg.

B. P. 14s-15o 0. at 4 mm. Hg. M. P. oi methlodide: 92-93" C.

}M P. of methiodide: 85 C.

}B. P. 165168 c. at 6 mm. Hg.

B. P. 150-154 C. at 2 mm. Hg. M. P. of methiodide: 87-88 C.

}M. P. of hydroch1oride:9394 C.

B. P. 155158 C. at 3 mm. Hg. M. P. of methiodide: 103-105 C.

}B. P. 152-153 C. at 2 mm. Hg. CH:

1 P. of hydrochloride: 92 C.

}B. P. 170-173 C. at 2 mm.- Hg.

}B. P. 160-165" C. at 8 mm. Hg.

What I claim and desire to secure by Letters Patent is:

1. The a-phenyl-walerate of diethylamino ethanol having the formula CH.COO.CH2CH2N(C:H5)2

and its salts.

2. Process for the preparation of the a-phenylvalerate of diethylaminoethanol consisting in causing a member of the group consisting of the alkali metal salts and alkaline earth salts of a-phenyl-valeric acid to react with l-diethylamino-2-chlorethane.

3. Process for the preparation of the alphaphenyl-valerate of diethylaminoethanol consisting in condensing, in an acetone medium, alphaphenylvaleric acid with the hydrochloride of diethylamino-chlorethane, in the presence of an alkali-metal carbonate.

- PIERRE VIAUD. 

